Sie sind auf Seite 1von 6

Pulmonary and Critical Care Updates

Update in Community-acquired and Nosocomial


Pneumonia 2009
Antoni Torres
1
and Jordi Rello
2
1
Servicio de Neumolog a, Instituto Cl nico del Torax, Hospital Cl nic i Provincial de Barcelona-Institut dInvestigacions Biome`diques August Pi i
Sunyer, Universidad de Barcelona-Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Respiratorias, Barcelona; and
2
Servei de
Cures Intensives, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili-CIBER de Enfermedades Respiratorias, Tarragona, Spain
Community-acquired and nosocomial pneumonia are frequent
infectious problems that face clinicians in daily practice. Dif-
ferentiation between community-acquired pneumonia and nos-
ocomial pneumonia is based on different etiopathogenesis,
microbiology, diagnosis, treatment, and outcome. These are
strong reasons for presenting the new 2009 information sepa-
rately.
Community-acquired pneumonia (CAP) has an incidence
ranging between 3 and 40 per 1,000 inhabitants per year (in-
creasing with age), with rates of hospitalization between 40 and
60%. The rate at which patients with CAP are admitted to the
intensive care unit (ICU) is approximately 10%. The overall
mortality rate of hospitalized patients is 10%.
In the eld of CAPresearch, 2009 brought newinformation on
newguidelines, prognostic scales for hospital and ICUadmission,
the utility of biomarkers for tailoring antibiotics and outcome
prediction, new microbiological causes of CAP including H1N1
virus, advances toward better antibiotic treatment, and important
clinical evidence regarding risk and prognosis factors.
Nosocomial pneumonia (NP) is frequent in intensive care
units, especially inpatients intubatedfor more than48 hours, with
an approximate incidence of 20% and of 10 to 15 per 1,000 days
of mechanical ventilation. Whennosocomial pneumonia presents
in mechanically ventilated patients it is known as ventilator-
associated pneumonia (VAP). The attributable mortality is ap-
proximately 30%, although this gure is not universally accepted.
Preventing NPand VAPis the most cost-effective measure in this
type of infection, and we have focused our 2009 review of NP and
VAP on this topic. A rich body of new information regarding
prevention was gathered in 2009; this information includes new
guidelines, andinsights onposition, oral care, endotracheal tubes,
noninvasive mechanical ventilation, and most especially, bundles
for implementation.
COMMUNITY-ACQUIRED PNEUMONIA
Guidelines
At the end of 2009 the British Thoracic Society guidelines for the
management of CAP in adults (1) were published. These excel-
lent recommendations are based on a straightforward search of
the literature and a sound system of evidence of grading.
However, they did not include information published during
2009. They differ from the last Infectious Diseases Society of
America/American Thoracic Society (IDSA/ATS) guidelines (2)
in the following main aspects: (1) preference for the CRB-65
(instead of the Pneumonia Severity Index [PSI]) prognostic scale
to assess severity, (2) inclusion of C-reactive protein for non-
response assessment, (3) noncoverage of atypical microorgan-
isms in patients with low-severity CAP, (4) reservation of
quinolones as an alternative antibiotic treatment, and (5) recom-
mendation of a combination of a broad-spectrum b-lactamase
withclarithromycin for severe CAP. Our mainconcernwiththese
recommendations is the lack of coverage of atypical microorgan-
isms, because they are frequent in patients with low-severity
disease. In addition, Legionella pneumophila may cause pneu-
monia in all class severities.
The American Academy of Emergency Medicine has pub-
lished a white paper (3) and position statement on the measure-
ment of time to rst antibiotic for pneumonia in emergency
departments. The main conclusion of this position paper is that
the measurement of time to rst antibiotic dose, because of the
inconsistent results (class Cindication) andoveruse of antibiotics,
must be discontinued. In our opinion this statement is too drastic
and disregards all the consistent information about patients with
CAP and sepsis (see below). This subset of patients with CAP,
probably the target population for this measure, may represent
more than 30% of patients arriving with CAP at emergency
departments (4).
Prediction of Mortality/Criteria for Hospital and
ICU Admission
Criteria for hospital or ICUadmission determine one of the most
important decisions in the management of CAP. The PSI and
CURB-65 prognostic scales have been extensively validated and
show similar results for the prediction of 30-day mortality.
Capelastegui and colleagues (5) validated a newprognostic index
for 90-day mortality (published in Thorax). This score allows
clinicians to stratify patients into three categories of 90-day
mortality: low risk (3.5%), intermediate risk (17.2%), and high
risk (43.5%). The 2007 IDSA/ATS guidelines (2) issued major
and minor criteria for patients with CAP admitted to the ICU;
these criteria were validated in 2009 (6). One of the pending
questions concerns the early detection of patients with severe
CAP who do not present major evidence (need for mechanical
ventilation or septic shock) for ICU admission. In this regard,
Renaud and colleagues (7) developed an international prediction
rule including 11 variables with different assigned scores. The
area under the curve was 0.81 for the overall population. In-
terestingly, one observational study conrms the independent
(Received in original form January 8, 2010; accepted in nal form February 8, 2010)
Supported by 2009 SGR 911, CIBER de Enfermedades Respiratorias (CIBERES
CB06/06/0028); CIBERES is an initiative of ISCIII.
Correspondence and requests for reprints should be addressed to Antoni Torres,
M.D., Ph.D., Servei de Pneumologia, Villarroel 170, 08036 Barcelona, Spain. E-
mail: atorres@ub.edu; and Jordi Rello, M.D., Ph.D., Servei de Pneumologia,
Mallafre Guasch, 4, 43007 Tarragona, Spain. E-mail: jrello.hj23.ics@gencat.cat
This article has an online supplement, which is accessible from this issues table of
contents at www.atsjournals.org
Am J Respir Crit Care Med Vol 181. pp 782787, 2010
DOI: 10.1164/rccm.201001-0030UP
Internet address: www.atsjournals.org
value of thrombocytopenia (already known) and thrombocytosis
in predicting 30-day mortality (8). Hypoglycemia at admission
was also an independent factor associated with increased 30-day
mortality (odds ratio [OR], 2.25), along with need for mechanical
ventilation (OR, 3.8) and need for inotropic support (OR, 2.9), in
a prospective observational study (9).
Finally, Rello and colleagues (10) developed a severity-
assessment score based on the PIRO concept. The PIRO
(predisposition, insult, response, organ dysfunction) score per-
formed better than the APACHE (Acute Physiology And
Chronic Health Evaluation) II score and ATS/IDSA criteria
at predicting 28-day mortality. However, immunosuppression
was included as one of the predisposing factors and, in fact, all
previous information refers to nonimmunosuppressed patients.
Given all this available information, our recommendation is
to use the simple modied ATS criteria to decide on ICU
admission (7), as they performed as well as the new IDSA/ATS
criteria (2).
Biomarkers
The use of biomarkers in the management of CAP has gained
popularity. The most widely used biomarker is procalcitonin,
a hormokine released in serum in the presence of bacterial
infections. Schuetz and colleagues (11) reported in JAMAa non-
inferiority randomized trial for the utility of antibiotics in lower
respiratory tract infection, using a guidance protocol based on
several thresholds of procalcitonin compared with standard
management guidelines. The population included almost 70%
of patients withCAP. This strategy provided similar outcomes for
both arms of the study, but antibiotic exposure and antibiotic-
associated adverse effects were lower in the procalcitonin-guided
arm. Procalcitonin is also useful for predicting 30-day mortality
when associated with prognostic scales (12) and for predicting
clinical stability (13). In these latter two studies C-reactive
protein performed as well as procalcitonin. Other biomarkers
such as proadrenomedullin and copeptin are promising. Our
opinion is that the measurement of biomarkers should be in-
corporated into current guidelines for a better prediction of
mortality. The use of biomarkers to guide antibiotic treatment
in CAP needs to be conrmed by more investigators, in addition
to those of the Swiss group.
Diagnosis and Etiology
A controversial issue is the potential utility of blood cultures in
all hospitalized patients with CAP. Falguera and colleagues (14)
developed a simple clinical score to predict bacteremia, using
referrals and internal validation cohorts. The use of this score
may reduce the burden on the microbiology laboratory. Pneu-
mococcal pneumonia is the most frequent cause of CAP. A
higher genomic bacterial load of Streptococcus pneumoniae in
blood is associated with higher risk of septic shock and death in
that population.
Several studies published in 2009 provide important insights
regarding the microbial etiology of CAP: Mycoplasma pneumo-
niae is a frequent cause of CAPpresenting as low-severity disease
(15); community-acquired necrotizing pneumonia caused by
methicillin-resistant Staphylococcus aureus carrying the gene
for Panton-Valentine leukocidin is an emerging infection with
an incidence of 0.51 to 0.64 cases per 100,000 inhabitants (16);
nally, the incidence of Enterobacteriaceae (1.3%) and Pseudo-
monas aeruginosa (0.4%) is lowinhospitalizedpatients withCAP
when the health careassociated pneumonia population is ex-
cluded (17).
Health careassociated pneumonia should be considered
a distinct subset of pneumonia, associated with more severe
disease, longer hospital stay, and higher mortality rates (18), as
shown by Venditti and colleagues in the Annals of Internal
Medicine. Microbial etiology in the United States includes a high
percentage of methicillin-resistant S. aureus and P. aeruginosa;
these ndings do not agree with European data. As recommen-
ded by Brito and Niederman (19), we need a better stratication
of risk factors to cover multidrug resistance in health care
associated pneumonia. Our recommendation is that risk strati-
cation to cover multiresistant organisms in both CAP and health
careassociated pneumonia should be reviewed and updated.
Viruses that cause community-acquired pneumonia are often
overwhelmed by clinicians and are a frequent cause of mixed
CAP (associated with S. pneumoniae and H. inuenzae). These
mixed cases are more severe than cases due to monomicrobial
etiology. Understanding viralbacterial interactions is an im-
portant goal of basic animal and viral research to better prevent
CAP in the future (20, 21).
The H1N1 pandemic has given us the opportunity to observe
and treat severe pneumonia cases caused by this virus. Obser-
vational studies from Mexico (22), Australia and New Zealand
(23, 25), Canada (24), China (25), and Spain (26) have
characterized these cases: median age of 3035 years, morbid
obesity as a main risk factor, frequent need for mechanical
ventilation (70%), and development of adult respiratory distress
syndrome and overall mortality at 90 days of 18%. Reports
from the southern hemisphere have been extremely useful for
management of these patients in the northern hemisphere,
providing an example of how clinical science, when rapidly
reported, plays a key role in saving lives in this type of disease.
Treatment
Antimicrobial treatment includes several aspects, such as early
administration of the appropriate antibiotics, type and duration
of antibiotics, and, in the most severe cases, coadjuvant therapy.
Some insights into these issues were provided in 2009. For
example, in a prospective multicenter, observational study,
Ferrer and colleagues (27) showed that early administration of
antibiotics is the most benecial approach in terms of survival of
patients with severe sepsis (30% of patients with pneumonia).
Analyses from Community-acquired Pneumonia Organization
data in elderly patients with CAP (28) also conrmed the
benecial effects on outcome (between 17 and 8% mortality)
when physicians adhered to empirical antibiotic treatment rec-
ommended by the IDSA/ATS guidelines. In terms of the type of
antibiotic treatment, two prospective studies suggest that adding
macrolides to b-lactams results in better mortality when com-
pared with b-lactam single-drug therapy in hospitalized patients
with CAP (29) or when compared with the combination of
b-lactam plus quinolone in patients with CAP admitted to the
ICU (30). Targeted treatment is always recommended in CAP.
However, in a prospective randomized study, Falguera and
colleagues (14) found a lower percentage of relapses in patients
treated empirically compared with 25 patients in whom targeted
treatment was based on urinary antigen results (S. pneumoniae
and L. pneumophila). The explanation for these striking ndings
is that the overall accuracy of urinary antigens does not exceed
70%.
Coadjuvant therapies aimed at modulating increased inam-
matory or hypercoagulability states are potential coadjuvant
treatments for severe CAP. In 2009, Laterre and colleagues (31)
reported negative results of a post-hoc analysis of patients with
severe CAP from a phase III study of severe sepsis comparing
tifacogin (human tissue factor pathway inhibitor) with placebo.
In a small randomized trial of severe sepsis (39 patients, with
50% of the patients having pneumonia), administration of
Pulmonary and Critical Care Updates 783
granulocyte-macrophage colony-stimulating factor (which re-
verses monocyte deactivation) resulted in improved outcomes
(but not mortality) compared with a placebo (32). This strategy
was aimed at reverting sepsis-associated immunosuppression.
Investigators have explored coadjuvant therapies against
S. pneumoniae infection in animal models. Administration of pro-
tein synthesis inhibitors leads to less inammation and increased
survival in a mouse model of inuenzavirus superinfected with
S. pneumoniae (a frequent clinical situation) (33). Another
positive approach explored by Witzenrath and colleagues (34)
was the administration of puried bacteriophage endolysin in
a mouse model of severe pneumococcal CAP. The administra-
tion of corticosteroids in CAP is a controversial issue. Snijders
and colleagues (35) performed a randomized double blinded
clinical trial comparing the administration of corticosteroids plus
antibiotics with antibiotics alone. There were not differences in
outcome. However, the inclusion of patients with very severe
CAP (which should be the target population) was low. Conse-
quently, the results of this study do not solve the controversy of
administrating corticosteroids in severe CAP.
Risk, Prognosis, and Prevention
Among the risk factors for acquiring community-acquired pneu-
monia, previous treatment with inhaled steroids has been a mat-
ter of debate, particularly in patients with chronic obstructive
pulmonary disease. In 2009, Sin and colleagues (36) published
a meta-analysis of individual data on 7,042 patients (3,801 re-
ceived inhaled budesonide and 3,241 control treatment). The
results of the study showed that treating patients with chronic
obstructive pulmonary disease for 12 months withbudesonide did
not increase the risk of acquiring CAP in these patients. In terms
of prognosis, a large study from Germany (37) provides reliable
data on the mortality of hospitalized patients with CAP. Overall
mortality was 14% but decreased to 8% (a more realistic gure)
when nursing home and chronically bedridden patients were
excluded. This study, again, suggests that patients with health
careassociated pneumonia are a different population, at least in
terms of mortality. Two studies from the same group (Clinical
Research, Investigation, and Systems Modeling of Acute Illness
[CRISMA]) found more intimate and individual mechanisms to
explain worse outcomes in CAP. In one of these studies (38), the
lower 30-day, 90-day, and 1-year survival in CAP was associated
with increased systemic inammation and brinolysis and de-
creased antithrombin III and factor IX. In the other study (39),
high expression of the C-macrophage migration inhibitory factor
allele was associated with lower 90-day mortality.
Prevention of pneumococcal pneumonia was comprehen-
sively reviewed by Van der Poll and Opal in the Lancet (40).
Both inuenza and S. pneumoniae vaccination were shown to be
useful for this purpose. The covalently linked polysaccharide
S. pneumoniae vaccine has been in use for almost 10 years and has
been successful. The seven-valent conjugate vaccine has reduced
the incidence of invasive disease in children. Despite the effec-
tiveness of the conjugated vaccines, disturbing patterns in the
epidemiology of the disease are nowobserved, with an increase in
invasive disease attributable to nonvaccine serotypes. Serotype
19A is the most important concern. An expanded conjugated
vaccine including serotypes not covered in the present vaccines
might be useful.
Nosocomial Pneumonia
There is a striking paradox in the literature supporting high-
prole measures to reduce ventilator-associated pneumonia
(VAP): many studies show reductions in VAP rates but almost
none show any impact on the length of time patients spend on
mechanical ventilation, length of stay in the intensive care unit
or hospital, or mortality. VAP prevention measures that work
by reducing bacterial colonization preferentially lower the
frequency of these mislabeled, more benign events. The para-
dox makes changes in VAP rates alone an unreliable measure
of whether VAP prevention measures are truly benecial to
patients (41).
Mosier and Pham (42) reported an evidence-based recom-
mendation for the prevention, diagnosis, and treatment of VAP
in adult burn patients.
Many controversies still remain in the management of
hospital-acquired pneumonia and VAP (43). Three European
societiesthe European Respiratory Society, the European
Society of Intensive Care Medicine, and the European Society
of Clinical Microbiology and Infectious Diseaseswere inter-
ested in producing a document on hospital-acquired pneumonia
and VAP with a European perspective (44). They chose
controversial topics in the eld and others that were not covered
by the latest IDSA/ATS guidelines. The panel dened 20
consensual points that were circulated several times among
the members of the panel until total agreement was reached. A
combination of evidence and clinical-based medicine was used
to reach this consensus.
Ventilator-associated pneumonia has been poorly studied in
Africa, but is likely to be a signicant problem, with resulting
increased morbidity and mortality in the pediatric intensive care
unit population. This guideline (45) aims to review the evidence
and recommendations for prevention and management of VAP
in children and to provide, where possible, clear advice to aid
the care of these children, and to limit costly and unnecessary
therapies. Evidence-based practical clinical guidelines are pro-
vided for South Africa.
Risk factors for VAP are multiple and susceptible to in-
tervention. A multidisciplinary team of authors (46) reviewed
these factors and identied those most susceptible to interven-
tion by nonpharmacological measures. They emphasized the
importance of oral and airway care and the critical role of
respiratory therapists and nurses. In addition, hand hygiene in
health care workers and regular oral care with chlorhexidine are
viewed as important measures for VAP prevention, as pre-
sented in this well-conducted review (46).
A visionary article by Craven (47) provides highlights from
guidelines and publications discussing VAP prevention strate-
gies and examining barriers to their implementation. Prevention
and implementation of cost-effective strategies to reduce risk
and improve patient outcomes should be prioritized. Clearly,
prevention programs should be specic and may vary among
hospitals, but a multidisciplinary prevention team with a leader
should be set up to establish priorities, and benchmarking goals,
to analyze data, and to sow the seeds of change for risk
reduction.
A randomized clinical trial with blinded outcome assessment
was conducted in 262 consecutive patients in a medicalsurgical
intensive care unit of a cancer hospital in Brazil (48). Closed
tracheal suction systems with heat and moisture exchangers
were used with both groups and were changed regularly. All
patients were nursed with backrest elevation to 45 degrees.
Medical or surgical personnel, who were blinded to group
allocations, requested suctioning when any of the following
occurred: visible or audible secretions, ventilatorpatient asyn-
chrony, or increased peak inspiratory pressures or decreased
tidal volumes attributed to secretions. Respiratory therapists
performed the suctioning according to a standardized procedure
that included preoxygenation. The therapist instilled 8 ml of
normal saline before suctioning in the intervention group only.
784 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 181 2010
Signicantly fewer patients in the saline group (14 of 130)
developed VAP than in the control group (31 of 132): relative
risk reduction, 0.54 (95% condence interval [CI], 0.180.74).
This indicates that one patient will avoid developing VAP for
every eight patients in whom saline instillation is used. Signif-
icant benets of saline infusion were also seen in the incidence
of microbiologically proven VAP (9 vs. 21 per 1,000 days of
mechanical ventilation; P 5 0.01) and in the time to rst VAP
(P 5 0.02). The groups did not differ signicantly in terms of
secondary outcomes.
Shorr and colleagues (49) conducted a cost-effectiveness
analysis of the economic outcomes of VAP prevention associ-
ated with silver-coated endotracheal tubes. Authors used a sim-
ple decision model based on a hypothetical 1,000-patient cohort
intubated with silver-coated or uncoated tubes. After multiple
analyses, the authors concluded that the silver-coated endotra-
cheal tubes represented a strategy for preventing VAP that may
yield hospital savings.
Two studies investigated the impact of patient position on
the incidence of VAP. Alexiou and colleagues (50) performed
a systematic search for randomized control trials and analyzed
data extracted from three randomized control trials studying the
semirecumbent 45 degree position and four randomized control
trials studying the prone position with a total of 337 and 1,018
patients, respectively. The odds of developing VAP were
signicantly lower among patients in the semirecumbent, 45
degree position compared with the supine position (OR, 0.46;
95% CI, 0.270.82). The comparison between prone and supine
positions showed a moderate trend toward better outcomes
regarding the incidence of clinically diagnosed VAP among
patients in the prone position (OR, 0.80; 95% CI, 0.601.08). An
additional study (51) indicated that the prone position did not
protect against the risk of VAP.
Several studies evaluated the effect of various hygiene
techniques for VAP prevention. Popovich and colleagues (52)
examined the effectiveness of patient cleansing with chlorhex-
idine (CHX) on rates of nosocomial infection. Bathing with
CHX was associated with a signicant decrease in the rate of
central venous catheterassociated bloodstream infections and
in the rate of blood culture contamination, but rates of VAP did
not change signicantly.
Hutchins and colleagues (53) reported a quality improve-
ment project, based on a combined technique of oral care with
a suction toothbrush, and cleansing of the oral cavity with
suction swabs treated with hydrogen peroxide. After the instate-
ment of the quality-improvement project, VAP rates decreased
from 12.6 cases per 1,000 ventilator days to 4.12.
Koeman and colleagues (54) enrolled patients requiring
mechanical ventilation for 48 hours or more in a randomized,
double-blind, placebo-controlled trial with three arms: chlo-
rhexidine (CHX 2%), chlorhexidinecolistin (CHX/COL), and
placebo (PLAC). The daily risk of VAP was reduced in both
interventional arms when compared with the placebo group.
Unfortunately, no differences in duration of mechanical venti-
lation, intensive care unit stay, or intensive care unit survival
could be demonstrated.
Pobo and colleagues (55) reported a simple, blind prospective
randomized trial of adult patients intubated for more than
48 hours. Patients were randomized to oral care every 8 hours
with 0.12% CHX digluconate (standard group) or standard oral
care plus electric tooth brushing. After an interim analysis, the
toothbrush group and standard group had comparable rates of
VAP: The groups did not differ in mortality, antibiotic-free days,
duration of mechanical ventilation, and ICU length of stay.
Authors concludedthat toothbrushing didnot improve a strategy
of standard oral care with CHX. Another negative study (56)
conrmed that 7-day ventilator circuit change did not contribute
to increased rates of VAP in a pediatric ICU, thereby conrming
that it may be used to save on workload and supply costs.
A prospective, randomized study (57) randomized patients to
receive enteral feeding. One group received nasoduodenal (ND)
feeding and the other group received nasogastric (NG) feeding.
Results showed that the ND group had higher average daily
calorie and protein intake compared with the NG group and
achieved nutritional goals earlier. The ND feeding group also had
a lower rate of vomiting and VAP in the medical ICU setting.
An important controversy is whether early versus late
tracheostomy is of benet in developing VAP. This study (58)
included 158 ICU patients more than 65 years of age who
underwent tracheotomy.
The early tracheotomy group included 43 patients and 115
patients were included in the late group. A statistically signif-
icant difference in the rate of VAP was observed in the early
tracheotomy group (20.29% VAP; 95% CI, 20.46 to 20.12),
suggesting that early tracheostomy in elderly patients is associ-
ated with less VAP.
A promising group of studies reviewed the value of care
bundles to prevent VAP (59, 60). The Institute of Healthcare
Improvement (Cambridge, MA) has led the change with its
ventilator bundle aimed at VAP prevention. In a systematic
literature review (59), four studies met the inclusion criteria. The
review revealed major methodological aws in design, reporting,
and results of the studies, including bias, confounding, and lack of
generalizability. These authors concluded that the ventilatory
bundle is not a viable quality measure in the intensive care unit at
this time.
The standard ventilatory bundle was modied (60) to include
a group of respiratory therapistdriven protocols, and postim-
plementation observed a signicant reduction in VAP from
a median of 14.1 cases per 1,000 ventilator days. Another study
(61) assessed whether the implementation of an electronic
dashboard would improve compliance with the bundle parame-
ters and reduce rates of VAP in a surgical ICU. Average
compliance with the ventilator bundles improved from 39% in
August 2007 to 89% in July 2008 (P , 0.01). Rates of VAP
decreased from a mean of 15.2 to 9.3 events per 1,000 ventilator
days after introduction of the dashboard (P , 0.01). This study
suggests that implementation of an electronic dashboard im-
proves compliance with a ventilatory bundle and may reduce
rates of VAP.
A modied ventilatory bundle, including oral care and
subglottic secretion drainage, was implemented in a Brazilian
hospital (62). Their ndings suggest that reducing VAP to zero
is not feasible and reduction involves multiple performance
measures and interventions.
An excellent review assessed the value of care bundles (63)
in preventing VAP. The authors concluded that the ventilator
bundle was an effective method for reducing VAP rates in
ICUs. However, they suggested that the ventilator bundle
should be modied and expanded to include specic processes
of care that have been denitively shown to be effective in
VAP reduction or a specic VAP bundle created to focus on
VAP prevention. Interestingly, a European panel of experts
developed a prevention bundle based on evidence from Euro-
pean guidelines (64). The original contribution is that authors
scored potential variables, using multi-criteria decision analysis.
Five variables, including oral care and sedation control, were
recommended. Further studies have to validate the European
care bundle in a clinical setting.
Avoiding intubation or reintubation and shortening the
period of mechanical ventilation are measures included in
bundles for VAP prevention. Noninvasive mechanical venti-
Pulmonary and Critical Care Updates 785
lation may avoid intubation or reintubation with the conse-
quent shortening the period of mechanical ventilation. In
a randomized trial published in the Lancet (65), Ferrer and
colleagues demonstrated that noninvasive mechanical ventila-
tion applied in extubated patients with chronic respiratory
disorders who developed hypercapnia during the T-piece trial
decreases the rate of reintubation, VAP, and mortality at 90
days.
Conict of Interest Statement: A.T. has received consultancy fees from Astellas,
Bayer, and Covidien (all for $1,001$5,000); he has received advisory board fees
from Astellas ($1,001$5,000); he has received industry-sponsored grants from
Pzer ($10,001$50,000). J.R. has no nancial relationship with a commercial
entity that has an interest in the subject of this manuscript.
References
1. Lim WS, Baudouin SV, George RC, Hill AT, Jamieson C, Le Jeune I,
Macfarlane JT, Read RC, Roberts HJ, Levy ML, Wani M, Woodhead
MA, et al. BTS guidelines for the management of community-
acquired pneumonia in adults. Thorax 2009;64:iii1iii55.
2. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD,
Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, et al.;
Infectious Diseases Society of America, American Thoracic Society.
Infectious Diseases Society of America/American Thoracic Society
consensus guidelines on the management of community-acquired
pneumonia in adults. Clin Infect Dis 2007;44:S27S72.
3. Pines JM. Isserman JA, Hinfey PB. The measurement of time to rst
antibiotic dose for pneumonia in the emergency department: a white
paper and position statement prepared for the American Academy of
Emergency Medicine. J Emerg Med 2009;37:335340.
4. Dremsizov T, Clermont G, Kellum JA, Kalassian KG, Fine MJ, Angus
DC. Severe sepsis in community-acquired pneumonia: when does it
happen, and do systemic inammatory response syndrome criteria
help predict course? Chest 2006;129:968978.
5. Capelastegui A, Espan a PP, Quintana JM, Bilbao A, Menendez R,
Zalacain R, Torres A. Pneumonia. Thorax 2009;64:496501.
6. Liapikou A, Ferrer M, Polverino E, Balasso V, Esperatti M, Pin er R,
Mensa J, Luque N, Ewig S, Menendez R, et al. Severe community-
acquired pneumonia: validation of the Infectious Diseases Society of
America/American Thoracic Society guidelines to predict an inten-
sive care unit admission. Clin Infect Dis 2009;48:377385.
7. Renaud B, Labare` re J, Coma E, Santin A, Hayon J, Gurgui M, Camus
N, Roupie E, He mery F, Herve J, et al. Risk stratication of early
admission to the intensive care unit of patients with no major criteria
of severe community-acquired pneumonia: development of an in-
ternational prediction rule. Crit Care 2009;13:R54.
8. Mirsaeidi M, Peyrani P, Aliberti S, Filardo G, Bordon J, Blasi F,
Ramirez JA. Thrombocytopenia and thrombocytosis at time of
hospitalization predict mortality in patients with community-acquired
pneumonia. Chest 2010;137:416420.
9. Singanayagam A, Chalmers JD, Hill AT. Admission hypoglycaemia is
associated with adverse outcome in community-acquired pneumonia.
Eur Respir J 2009;34:932939.
10. Rello J, Rodriguez A, Lisboa T, Gallego M, Lujan M, Wunderink R.
PIRO score for community-acquired pneumonia: a new prediction
rule for assessment of severity in intensive care unit patients with
community-acquired pneumonia. Crit Care Med 2009;37:456462.
11. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M,
Widmer I, Neidert S, Fricker T, Blum C, Schild U et al.; ProHOSP
Study Group. Effect of procalcitonin-based guidelines vs. standard
guidelines on antibiotic use in lower respiratory tract infections: the
ProHOSP randomized controlled trial. JAMA 2009;302:10591066.
12. Mene ndez R, Martnez R, Reyes S, Mensa J, Filella X, Marcos MA,
Martnez A, Esquinas C, Ramirez P, Torres A. Biomarkers improve
mortality prediction by prognostic scales in community-acquired
pneumonia. Thorax 2009;64:587591.
13. Mene ndez R, Martinez R, Reyes S, Mensa J, Polverino E, Filella X,
Esquinas C, Martinez A, Ramirez P, Torres A. Stability in community-
acquired pneumonia: one step forward with markers? Thorax 2009;64:
987992.
14. Falguera M, Ruiz-Gonza lez A, Schoenenberger JA, Touzon C, Ga zquez
I, Galindo C, Porcel JM. Prospective, randomized study to compare
empirical treatment versus targeted treatment on the basis of the
urine antigen results in hospitalized patients with community-
acquired pneumonia. Thorax 2010;65:101106.
15. Rello J, Lisboa T, Lujan M, Gallego M, Kee C, Kay I, Lopez D, Waterer
GW; DNA-Neumococo Study Group. Severity of pneumococcal
pneumonia associated with genomic bacterial load. Chest 2009;136:
832840.
16. Vardakas KZ, Matthaiou DK, Falagas ME. Incidence, characteristics
and outcomes of patients with severe community acquired-MRSA
pneumonia. Eur Respir J 2009;34:11481158.
17. Von Baum H, Welte T, Marre R, Suttorp N; S. Ewig; CAPNETZ Study
Group. Community-acquired pneumonia through Enterobacteriaceae
and Pseudomonas aeruginosa: diagnosis, incidence and predictors.
Eur Respir J 2010;35:598615.
18. Venditti M, Falcone M, Corrao S, Licata G, Serra P; Study Group of the
Italian Society of Internal Medicine. Outcomes of patients hospital-
ized with community-acquired, health careassociated, and hospital-
acquired pneumonia. Ann Intern Med 2009;150:1926.
19. Brito V, Niederman MS. Healthcare-associated pneumonia is a hetero-
geneous disease, and all patients do not need the same broad-
spectrum antibiotic therapy as complex nosocomial pneumonia. Curr
Opin Infect Dis 2009;22:316325.
20. Sajjan U, Wang Q, Zhao Y, Gruenert DC, Hershenson MB. Rhinovirus
disrupts the barrier function of polarized airway epithelial cells. Am
J Respir Crit Care Med 2008;178:12711281.
21. Cho HY, Imani F, Miller-DeGraff L, Walters D, Melendi GA, Yama-
moto M, Polack FP, Kleeberger SR. Antiviral activity of Nrf2 in
a murine model of respiratory syncytial virus disease. Am J Respir
Crit Care Med 2009;179:138150.
22. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez
M, Quin ones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-
Serrano J, Ormsby CE, Corrales A, et al.; INER Working Group
on Inuenza. Pneumonia and respiratory failure from swine-origin
inuenza A (H1N1) in Mexico. N Engl J Med 2009;361:680689.
23. Webb SA, Pettila V, Seppelt I, Bellomo R, Bailey M, Cooper DJ,
Cretikos M, Davies AR, Finfer S, Harrigan PW, et al.; ANZIC
Inuenza Investigators. Critical care services and 2009 H1N1 in-
uenza in Australia and New Zealand. N Engl J Med 2009;361:1925
1934.
24. Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J,
Stelfox T, Bagshaw S, Choong K, Lamontagne F, et al.; Canadian
Critical Care Trials Group H1N1 Collaborative. Critically ill patients
with 2009 inuenza A (H1N1) infection in Canada. JAMA 2009;302:
18721879.
25. Cao B, Li XW, Mao Y, Wang J, Lu HZ, Chen YS, Liang ZA, Liang L,
Zhang SJ, Zhang B, et al.; National Inuenza A Pandemic (H1N1)
2009 Clinical Investigation Group of China. Clinical features of the
initial cases of 2009 pandemic inuenza A (H1N1) virus infection in
China. N Engl J Med 2009;361:25072517.
26. Rello J, Rodrguez A, Iban ez P, Socias L, Cebrian J, Marques A,
Guerrero J, Ruiz-Santana S, Marquez E, Del Nogal-Saez F, et al.;
H1N1 SEMICYUC Working Group. Intensive care adult patients
with severe respiratory failure caused by inuenza A (H1N1) virus in
Spain. Crit Care 2009;13:R148.
27. Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A,
Pe rez XL, Sirvent JM; Edusepsis Study Group. Effectiveness of
treatments for severe sepsis: a prospective, multicenter, observational
study. Am J Respir Crit Care Med 2009;180:861866.
28. Arnold FW, LaJoie AS, Brock GN, Peyrani P, Rello J, Mene ndez R,
Lopardo G, Torres A, Rossi P, Ramirez JA; Community-acquired
Pneumonia Organization (CAPO) Investigators. Improving outcomes
in elderly patients with community-acquired pneumonia by adhering
to national guidelines: Community-Acquired Pneumonia Organiza-
tion International Cohort Study results. Arch Intern Med 2009;169:
15151524.
29. Tessmer A, Welte T, Martus P, Schnoor M, Marre R, Suttorp N. Impact
of intravenous b-lactam/macrolide versus b-lactam monotherapy on
mortality in hospitalized patients with community-acquired pneumo-
nia. J Antimicrob Chemother 2009;63:10251033.
30. Martin-Loeches I, Lisboa T, Rodriguez A, Putensen C, Annane D,
Garnacho-Montero J, Restrepo MI, Rello J. Combination antibiotic
therapy with macrolides improves survival in intubated patients with
community-acquired pneumonia. Intensive Care Med 2010;36:612
620.
31. Laterre PF, Opal SM, Abraham E, LaRosa SP, Creasey AA, Xie F,
Poole L, Wunderink RG. A clinical evaluation committee assessment
of recombinant human tissue factor pathway inhibitor (tifacogin) in
patients with severe community-acquired pneumonia. Crit Care 2009;
13:R36.
786 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 181 2010
32. Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J,
Weber-Carstens S, Hasper D, KehD, ZuckermannH, et al. Granulocyte-
macrophage colony-stimulating factor to reverse sepsis-associated
immunosuppression: a double-blind, randomized, placebo-controlled
multicenter trial. Am J Respir Crit Care Med 2009;180:640648.
33. Karlstro m A, Boyd KL, English BK, McCullers JA. Treatment with
protein synthesis inhibitors improves outcomes of secondary bacterial
pneumonia after inuenza. J Infect Dis 2009;199:311319.
34. Witzenrath M, Gutbier B, Schmeck B, Tenor H, Seybold J, Kuelzer R,
Grentzmann G, Hatzelmann A, van Laak V, Tschernig T, et al.
Phosphodiesterase 2 inhibition diminished acute lung injury in murine
pneumococcal pneumonia. Crit Care Med 2009;37:584590.
35. Snijders D, Daniels JM, de Graaff CS, van der Werf TS, Boersma WG.
Efcacy of corticosteroids in community-acquired pneumonia: a ran-
domized double blinded clinical trial. Am J Respir Crit Care Med
2010; doi: 10.1164/rccm.200905-0808OC
36. Sin DD, Tashkin D, Zhang X, Radner F, Sjo bring U, Thore n A,
Calverley PM, Rennard SI. Budesonide and the risk of pneumonia:
a meta-analysis of individual patient data. Lancet 2009;374:712719.
37. Ewig S, Birkner N, Strauss R, Schaefer E, Pauletzki J, Bischoff H,
Schraeder P, Welte T, Hoeffken G. New perspectives on community-
acquired pneumonia in 388 406 patients: results from a nationwide
mandatory performance measurement programme in healthcare
quality. Thorax 2009;64:10621069.
38. Reade MC, Yende S, DAngelo G, Kong L, Kellum JA, Barnato AE,
Milbrandt EB, Dooley C, Mayr FB, Weissfeld L, et al.; Genetic and
Inammatory Markers of Sepsis Investigators. Differences in immune
response may explain lower survival among older men with pneumo-
nia. Crit Care Med 2009;37:16551662.
39. Yende S, Angus DC, Kong L, KellumJA, Weissfeld L, Ferrell R, Finegold
D, Carter M, Leng L, Peng ZY, et al. The inuence of macrophage
migration inhibitory factor gene polymorphisms on outcome from
community-acquired pneumonia. FASEB J 2009;23:24032411.
40. Van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of
pneumococcal pneumonia [review]. Lancet 2009;374:15431556.
41. Klompas M. The paradox of ventilator-associated pneumonia preven-
tion measures. Crit Care 2009;13:315.
42. Mosier MJ, Pham TN. American Burn Association practice guidelines
for prevention, diagnosis, and treatment of ventilator-associated
pneumonia (VAP) in burn patients. J Burn Care Res 2009;30:
910928.
43. Daz L, Llaurado M, Rello J, Restrepo MI. Non-pharmacological
prevention of ventilator associated pneumonia. Arch Bronconeumol
200; doi: 10.1016/j.arbres.2009.08.001.
44. Torres A, Ewig S, Lode H, Carlet J; European HAP Working Group.
Dening, treating and prevention hospital acquired pneumonia:
European perspective. Intensive Care Med 2009;35:929.
45. Morrow BM, Argent AC, Jeena PM, Green RJ. Guideline for the
diagnosis, prevention and treatment of paediatric ventilator-associated
pneumonia. S Afr Med J 2009;99:255267.
46. Bouza E, Burillo A. Advances in the prevention and management of
ventilator-associated pneumonia. Curr Opin Infect Dis 2009;22:345351.
47. Craven DE. Preventing ventilator-associated pneumonia in adults:
sowing seeds of change. Chest 2006;130:251260.
48. Caruso P, Denari S, Ruiz SA, Demarzo SE, Deheinzelin D. Saline
instillation before tracheal suctioning decreases the incidence of
ventilator-associated pneumonia. Crit Care Med 2009;37:3238.
49. Shorr AF, Zilberberg MD, Kollef M. Cost-effectiveness analysis of a silver-
coated endotracheal tube to reduce the incidence of ventilator-associ-
ated pneumonia. Infect Control Hosp Epidemiol 2009;30:759763.
50. Alexiou VG, Lerodiakonou V, Dimopoulos G, Falagas ME. Impact of
patient position on the incidence of ventilator-associated pneumonia:
a meta-analysis of randomized controlled trials. J Crit Care 2009;24:
515522.
51. Mounier R, Adrie C, Franc xais A, Garrouste-Orgeas M, Cheval C,
Allaouchiche B, Jamali S, Dinh-Xuan AT, Goldgran-Toledano D,
Cohen Y, et al.; Outcomerea Study Group. Study of prone positioning
to reduce ventilator-associated pneumonia in hypoxemic patients.
Eur Respir J 2009; doi: 0.1183/09031936.00057509.
52. Popovich KJ, Hota B, Hayes R, Weinstein RA, Hayden MK. Effective-
ness of routine patient cleansing with chlorhexidine gluconate for
infection prevention in the medical intensive care unit. Infect Control
Hosp Epidemiol 2009;30:959963.
53. Hutchins K, Karras G, Erwin J, Sullivan KL. Ventilator-associated
pneumonia and oral care: a successful quality improvement project.
Am J Infect Control 2009;37:590597.
54. Koeman M, van der Ven AJ, Hak E, Jorre HC, Kaasajager K, de Smet
AG, Ramsay G, Dormans TP, Aarts LP, de Bel EE, et al. Oral
decontamination with chlorhexidine reduces the incidence of ventilator-
associated pneumonia. Am J Respir Crit Care Med 2006;173:1348
1355.
55. Pobo A, Lisboa T, Rodrguez A, Sole R, Magret M, Treer S, Go mez F,
Rello J; RASPALL Study Investigators. A randomized trial of dental
brushing for preventing ventilator-associated pneumonia. Chest 2009;
136:433439.
56. Samransamruajkit R, Jirapaiboonsuk S, Siritantiwat S, Tungsrijitdee O,
Deerojanawong J, Sritippayawn S, Prapphal N. Effect of frequency of
ventilator circuit changes (3 vs 7 days) on the rate of ventilator-
associated pneumonia in PICU. J Crit Care 2010;25:5661.
57. Hsu CW, Sun SF, Lin SL, Kang SP, Chu KA, Lin CH, Huang HH.
Duodenal versus gastric feeding in medical intensive care unit
patients: a prospective, randomized, clinical study. Crit Care Med
2009;37:18661872.
58. Schneider GT, Christensen N, Doerr TD. Early tracheotomy in elderly
patients results in less ventilator-associated pneumonia. Otolaryngol
Head Neck Surg 2009;140:250255.
59. Zilberberg MF, Shorr AF, Kollef MH. Implementing quality improve-
ments in the intensive care unit: ventilator bundle as an example. Crit
Care Med 2009;37:206209.
60. Blamoun J, Alfakir M, Rella ME, Wojcik M, Solis RA, Anees Khan M,
DeBari VA. Efcacy of an expanded ventilator bundle for the
reduction of ventilator-associated pneumonia in the medical intensive
care unit. Am J Infect Control 2009;37:172175.
61. Zaydfudim V, Dossett LA, Stamer JM, Arbogast PG, Feurer ID, Ray
WA, May AK, Pinson CW. Implementation of a real-time compliance
dashboard to help reduce SICU ventilator-associated pneumonia with
the ventilator bundle. Arch Surg 2009;144:656662.
62. Marra AR, Cal RG, Silva CV, Caserta RA, Paes AT, Moura DF Jr,
dos Santos OF, Edmmond MB, Dura o MS. Successful prevention
of ventilator-associated pneumonia in an intensive care setting. Am
J Infect Control 2009;37:619625.
63. Wip C, Napolitano L. Bundles to prevent ventilator-associated pneu-
monia: how valuable are they? Curr Opin Infect Dis 2009;22:159166.
64. Rello J, Masterton R, Lode H, Cornaglia G. A European care bundle for
prevention of ventilator-associated pneumonia. Intensive Care Med
2009; doi: 10.1007/s00134-010-1841-5.
65. Ferrer M, Sellare s J, Valencia M, Carrillo A, Gonza lez G, Badia JR,
Nicolas JM, Torres A. Non-invasive ventilation alter extubation in
hypercapnic patients with chronic respiratory disorders: randomised
controlled trial. Lancet 2009;374:10821088.
Pulmonary and Critical Care Updates 787